title: Regulatory expression of MMP-8/MMP-9 and inhibition of proliferation, migration and invasion in human lung cancer A549 cells in the presence of HGF variants.
abstract: Hepatocyte growth factor (HGF), a potent cytokine of mesenchymal origin, exhibits polytrophic physiological responses, including proliferation, migration, and invasion, in a wide variety of cells. Although it is known that inhibition of the responses by HGF variants was via signal transducers and activators of the transcription pathway, the mechanisms of action of the variants involved in the production of matrix metalloproteinases (MMPs) were not clearly understood. Thus, recombinant HGF variants, NK1, NK2, NK3, and NK4 were topically applied to assays for proliferation, migration, invasion, and expression of MMPs in the human lung cancer cell line A549 and compared to that of control medium and a glutathione-s-transferase control. Results showed that these recombinant HGF variants significantly inhibited proliferation, migration, and invasion of A549 at >4 nM, downregulated expression of MMP-9, and upregulated expression of MMP-8. The study clearly suggests that binding of the HGF variants to the cell surface c-Met resulted in the downregulation of MMP-9, and upregulation of MMP-8 protein expressions might be key molecular signals against proliferation, migration, and invasion of A549 cells.
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Ramanujum
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Jong-Kang
authors.initials: JK
authors.lastname: Liu
authors.forename: Shiping
authors.initials: S
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004926:Escherichia coli / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005982:Glutathione Transferase; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9
keywords: Invasion; Matrix metalloproteinase; Migration; N-terminus-kringle domains; Proliferation